Dostarlimab Combo Significantly Improves PFS in Advanced Endometrial Cancer

"[Endometrial cancer] is a disease where we had not achieved much, [but] all of a sudden, we see a tremendous, unprecedented benefit in improving patients’ [PFS], [OS], and their quality of life by seeing the patient-reported outcomes," according to Mansoor Raza Mirza, MD.

Treatment with dostarlimab-gxly (Jemperli) and chemotherapy followed by dostarlimab maintenance resulted in significant progression-free survival (PFS) benefit compared with chemotherapy alone among patients with advanced or recurrent endometrial cancer, according to the findings from the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO trial (NCT03981796).^1,2

Data from the trial, which were presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS), indicated that at a median follow-up of 25.4 months across the overall population, treatment with dostarlimab plus chemotherapy reduced the risk of disease progression or death compared with placebo plus chemotherapy (HR, 0.64; 95% CI, 0.507-0.800; P <.0001). In the dostarlimab and placebo arms, respectively, the PFS rate was 48.2% vs 29.0% at 12 months and 36.1% vs 18.1% at 24 months.

After a median follow-up of 24.8 months among patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) disease, the dostarlimab regimen produced a reduction in the risk of progression or death (HR, 0.28; 95% CI, 0.162-0.495; P <.0001). The 12-month and 24-month PFS rates in each respective arm were 63.5% vs 24.4% and 61.4% vs 15.7%.

With respect to overall survival (OS) in the overall population, dostarlimab plus chemotherapy reduced the risk of death (HR, 0.64; 95% CI, 0.464-0.870; P = .0021). In the dostarlimab and placebo arms, respectively, the OS rates were 84.6% vs 81.3% at 12 months, and 71.3% vs 56.0% at 24 months.

OS data in the dMMR/MSI-H cohort indicated that there was a reduction in the risk of death with the dostarlimab regimen (HR, 0.30; 95% CI, 0.127-0.699). Among patients who received dostarlimab and those treated with placebo in this population, respectively, the 12-month OS rates were 90.1% vs 79.6%, and the 24-month OS rates were 83.3% vs 58.7%.

Presenting author Mansoor Raza Mirza, MD, highlighted that PFS benefits with dostarlimab plus chemotherapy extended across all patient subgroups based on histology. Patients with endometrioid carcinoma, carcinosarcoma, serous adenocarcinoma, and other diseases experienced improved PFS outcomes with the dostarlimab regimen.

Mirza is the chief oncologist of the Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Denmark, and the medical director of the Nordic Society of Gynaecologic Oncology-Clinical Trial Unit (NSGO-CTU).

In the double-blind, multi-center RUBY trial, patients were randomly assigned 1:1 to receive 500 mg of dostarlimab intravenously or matched placebo plus carboplatin area under the curve 5 mg/mL per minute and 175 mg/m² of paclitaxel every 3 weeks for 6 cycles. Patients then continued to receive treatment with dostarlimab at 1000 mg or placebo every 6 weeks for up to 3 years.

The trial’s primary end points were investigator-assessed PFS per RECIST v1.1 guidelines and OS. Secondary end points included PFS2, objective response rate, duration of response, disease control rate, and safety.

Patients with stage III or IV endometrial cancer or first recurrent disease were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1 and adequate organ function. Patients also needed to be naïve to systemic anticancer treatment or have recurrent or progressive disease at 6 or more months after completing systemic therapy to enroll. Investigators stratified patients by MMR or MSI status, previous receipt of external pelvic radiotherapy, and disease status.

Among 400 patients with evaluable known molecular classifications, the HR for median PFS was not applicable (NA; 95% CI, NA-NA) with the dostarlimab or the placebo regimen among those with POLE mutations. However, Mirza noted that the dostarlimab regimen improved PFS among patients with dMMR/MSI-H disease (HR, 0.31; 95% CI, 0.17-0.56), TP53 mutations (HR, 0.55; 95% CI, 0.30-0.99), and those with no specific molecular profile (HR, 0.77; 95% CI, 0.55-1.07).

“[Endometrial cancer] is a disease where we had not achieved much, [but] all of a sudden, we see a tremendous, unprecedented benefit in improving patients’ [PFS], [OS], and their quality of life by seeing the patient-reported outcomes,” Mirza concluded.

References

1. Mirza MR. Dostarlimab in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: a placebo-controlled randomized phase 3 trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). Presented at 2023 Annual Global Meeting of the International Gynecologic Cancer Society; November 5-7, 2023; Seoul, Korea; abstract SE008/1309.
2. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388:2145-2158. doi:10.1056/NEJMoa2216334